As tests for genes that contribute to more diseases become available and, in many cases, become cheaper, we will increasingly be faced with decisions about how much we want to know about our future health prospects. Would you want to know if you carried a gene that conferred a 60% chance of developing Huntington's disease by age 65? Or that multiplied your chances of having a stroke by fiveeven though the risk of having a stroke in any given year would still be extremely low? How much would you pay for a test that, for more than 99.5% of women will reassure them that nothing is wrong, but in the other cases will reveal that one's odds of developing ovarian cancer are 39%? A prime example of this situation made the front page of the New York Times last monthand highlighted the deep connections that genetic testing has to the evolutionary history of human populations...

Where's the evolution?

The article in the Times described an ongoing debate in Israel about whether to institute a national screening campaign for aggressive breast cancer genes. Carrying a defective gene version multiplies a woman's odds of developing breast cancer by four or five. This debate is happening in Israel (and not in, say, Japan) because about half of the Jewish population of Israel is of Ashkenazi Jewish descent, tracing their ancestry to Jews from central and eastern Europe. Among this group, genes contributing to breast cancer are much more common than in the general population. The explanation for this lies in the evolutionary phenomena of founder events and bottlenecks.

In a founder event, a new population is begun from a small subset of individuals from a larger population. Because the new population starts with very few individuals, many gene versions (called alleles) that were present in the original population will not happen to be carried by members of the newly founded population. Thus, the new population starts with a subset of the genetic variation present in the larger population. On the flip side, any rare gene versions that, just by chance, happen to be carried by a member of the newly founded population will be overrepresented there. Furthermore, while the population is still small, these rare alleles can rise to even higher frequencies through the action of genetic drift, which has large effects on small populations. The result is that when the new population grows to a normal size again, it may wind up with very different gene frequencies than its parent population has and with many copies of some normally rare gene versions.

Through a similar mechanism, a population bottleneck can result in a population in which normally rare gene versions are common. In a bottleneck, a population's size is drastically reduced, and the population must rebuild itself from the surviving members. If the individuals that survive the bottleneck happen to carry any rare gene versions, these will be overrepresented in the descendent population and in the larger population that recovers from the bottleneck.

In the Ashkenazi ethnic group, the gene versions in question are three different, rare versions of BRCA1 and BRCA2, the so-called breast cancer genes. Two to two and a half percent of people of Ashkenazi descent carry at least one of these gene versionsa rate that is 10 to 50 times higher than in the population at large. Research suggests that these gene versions became relatively common in the Ashkenazi population through a combination of founder events and bottlenecks. During the Jewish Diaspora, around 75 A.D., a small number of Jewish people left the Middle East and founded the Ashkenazi population in Europe. Scientists aren't sure exactly how many original founders there were, but it was likely less than a few thousand of the many hundreds of thousands of Jews living in the Middle East at the time. While remaining largely isolated from the rest of the European population, the Ashkenazi population grew to at least 100,000. However, with the Crusades beginning in 1096, that population size was severely reduced. In the 1340s, with the Black Death, they suffered another serious hit. By 1350, the Jewish population of Europe had been reduced to fewer than 10,000, from which it again recovered. Through such founding events and bottlenecks, some very rare gene versionsincluding the BRCA variants in question, but also several others, including genes that cause Gaucher disease and Tay-Sachsrose to relatively high frequencies in the Ashkenazi population.

The evolutionary events of the past few thousand years have profoundly affected the genetic make-up of the Ashkenazi population todayas well as their personal health decisions and national health policy in Israel. Through genetic testing, many of these disease-contributing genes can be identified before they ever have a chance to make anyone ill. For example, in the case of Tay-Sachs (a disease that kills affected individuals before the age of four and that has no available treatments), people of Ashkenazi descent and others at high risk of carrying the recessive gene can be tested before having children and can manage their reproductive decisions based on that information. When it comes to the BRCA genes, potential carriers must weigh many options, including whether to test and whether to take action if a dangerous mutation is detected. Many carriers of the risky gene versions will never develop cancer at all; however, many others will develop potentially deadly breast cancers. Carriers may opt for a close monitoring strategy in the hopes of catching any cancer at an early, treatable stage, but many others will opt for preventative mastectomies to sharply reduce their odds of developing the disease. Such decisions aren't easy ones, but for many, knowing one's status as a carrier (or not) is a boon that allows them to optimize their health and life choices. And the evolutionary history of one's ancestors is a key component in determining that status.

In your own words, explain how a rare gene can become frequent through a population bottleneck.

What effect do founder events and bottlenecks have on the level of genetic variation in a population?

Advanced: Consider a hypothetical population in which a genetic disease is found to be quite common. The disease seems to have a rather small, but still negative, effect on an individual's capacity for reproduction. Besides founder events and bottlenecks, what else could explain the high frequency of the genes that cause this disease? Explain your hypothesis.

Related lessons and teaching resources

Teach about genetic drift and founder effects: In this lab for grades 13-16, students design and conduct experiments to evaluate whether evolution by natural selection may be induced in laboratory populations. Options are available for simulating genetic drift and founder effects.

Teach about human population genetics: This research profile for grades 13-16 follows statistician and population geneticist Emilia Huerta-Sánchez as she studies the adaptations that allow Tibetan highlanders to live 13,000 feet above sea level without developing altitude sickness.